DESCRIPTION: The overal goal of the work is to develop and test novel genetic methods to test the hypothesis that triple helix forming oligonucleotides can be used to deliver site-selective DNA damage and mutation in mammalian cells. The specific aims of the work are to develop new models to study triple helix- mediated mutagenesis (based upon shuttle vector technology), to investigate the physical parameters which affect targeted mutagenesis upon these shuttle vectors in vitro, to examine DNA damage and repair pathways which influence TFO mediated mutation, and finally to extend the work to study TFO mediated mutation in chromosomal genes of the mouse, rather than shuttle vectors.